PT  - JOURNAL ARTICLE
AU  - Yumiko Ishizawa
AU  - Ravindernath Pidikiti
AU  - Paul A. Liebman
AU  - Roderic G. Eckenhoff
TI  - G Protein-Coupled Receptors as Direct Targets of Inhaled Anesthetics
AID  - 10.1124/mol.61.5.945
DP  - 2002 May 01
TA  - Molecular Pharmacology
PG  - 945--952
VI  - 61
IP  - 5
4099  - http://molpharm.aspetjournals.org/content/61/5/945.short
4100  - http://molpharm.aspetjournals.org/content/61/5/945.full
SO  - Mol Pharmacol2002 May 01; 61
AB  - The molecular pharmacology of inhalational anesthetics remains poorly understood. Despite accumulating evidence suggesting that neuronal membrane proteins are potential targets of inhaled anesthetics, most currently favored membrane protein targets lack any direct evidence for anesthetic binding. We report herein the location of the binding site for the inhaled anesthetic halothane at the amino acid residue level of resolution in the ligand binding cavity in a prototypical G protein-coupled receptor, bovine rhodopsin. Tryptophan fluorescence quenching and direct photoaffinity labeling with [14C]halothane suggested an interhelical location of halothane with a stoichiometry of 1 (halothane/rhodopsin molar ratio). Radiosequence analysis of [14C]halothane-labeled rhodopsin revealed that halothane contacts an amino acid residue (Trp265) lining the ligand binding cavity in the transmembrane core of the receptor. The predicted functional consequence, competition between halothane and the ligand retinal, was shown here by spectroscopy and is known to exist in vivo. These data suggest that competition with endogenous ligands may be a general mechanism of the action of halothane at this large family of signaling proteins.